As­traZeneca’s big MYS­TIC tri­al ends a com­plete fail­ure as Imfinzi/treme­li­mum­ab com­bo flops on over­all sur­vival

Last year, As­traZeneca preached pa­tience af­ter ini­tial da­ta showed its check­point in­hibitor Imfinzi com­bined with their in-house CT­LA-4 drug failed to meet the pri­ma­ry end­point of pro­gres­sion-free sur­vival in a piv­otal lung can­cer tri­al. On Fri­day, that faith proved in vain as the im­munother­a­py al­so failed to im­prove over­all sur­vival in the keen­ly watched MYS­TIC tri­al.

The tri­al test­ed Imfinzi both as a monother­a­py and in com­bi­na­tion with an­oth­er check­point in­hibitor, treme­li­mum­ab, against chemother­a­py in treat­ment-naive pa­tients with stage IV non-small cell lung can­cer (NSCLC), a cru­cial are­na in the bat­tle for check­point drug dom­i­nance.

The phar­ma gi­ant $AZN con­ced­ed Fri­day morn­ing that the com­bi­na­tion — once con­sid­ered a cor­ner­stone of As­traZeneca’s check­point de­vel­op­ment strat­e­gy — ac­tu­al­ly per­formed worse than Imfinzi alone for the over­all sur­vival end­point, with a haz­ard ra­tio of 0.76 for the so­lo drug com­pared to an ane­mic 0.85 for the two to­geth­er.

Sean Bo­hen

While As­traZeneca’s pipeline has of­ten come up short, there have been a string of ma­jor suc­cess­es in on­col­o­gy for the com­pa­ny. This tri­al was con­sid­ered crit­i­cal in putting the brakes on the blitz­ing gains Mer­ck $MRK and Bris­tol-My­ers Squibb have made af­ter es­tab­lish­ing their lead in the lu­cra­tive front­line can­cer field. The study was al­so tout­ed by CEO Pas­cal So­ri­ot as an in­di­ca­tor of the British drug­mak­er’s val­ue as an in­de­pen­dent en­ti­ty, when it spurned Pfiz­er’s $PFE $118 bil­lion takeover bid in 2014

In a state­ment on Fri­day, As­traZeneca al­so sug­gest­ed that al­though sta­tis­ti­cal sig­nif­i­cance for over­all sur­vival had not been met, the da­ta mer­it­ed fur­ther analy­sis in ex­plorato­ry sub­groups. That’s not like­ly go­ing to in­spire much en­thu­si­asm.

Brad Lon­car

In MYS­TIC, “CT­LA-4 tru­ly of­fered no ben­e­fit or sig­nal at all”, said Brad Lon­car, man­ag­er of the Lon­car Can­cer Im­munother­a­py ETF. “I would think hard about these re­sults if I was one of the com­pa­nies out there de­vel­op­ing me-too or me-bet­ter CT­LA-4s (of which there are many). Giv­en its tox­i­c­i­ty pro­file and now the emerg­ing com­bo ef­fi­ca­cy we are see­ing in some of these can­cers out­side of melanoma, its win­dow is look­ing quite nar­row.”

As­traZeneca’s shares were al­so un­der pres­sure again on the fail­ure. Its stock is down more than 3% in pre-mar­ket trad­ing. Shares fell sharply last year on the PFS miss, evap­o­rat­ing some $14 bil­lion off the com­pa­ny’s val­ue.

Since that ini­tial set­back on MYS­TIC, though, As­traZeneca scored a big win with its PA­CIF­IC tri­al for Imfinzi, win­ning a sig­nif­i­cant mar­ket niche for it­self in stage III NSCLC. But the fail­ure here will sting, nev­er­the­less.

Chief med­ical of­fi­cer Sean Bo­hen spot­light­ed the suc­cess on the monother­a­py side, but con­ced­ed the key fail­ure:

We are en­cour­aged to see that Imfinzi monother­a­py ac­tiv­i­ty is in-line with that of the an­ti-PD-1 class in pre­vi­ous­ly-un­treat­ed pa­tients with Stage IV non-small cell lung can­cer; how­ev­er, we are dis­ap­point­ed that these re­sults missed sta­tis­ti­cal sig­nif­i­cance. We re­main con­fi­dent in Imfinzi as the cor­ner­stone of our IO pro­gramme and con­tin­ue to eval­u­ate its po­ten­tial in on­go­ing non-small cell lung can­cer tri­als, in­clud­ing Imfinzi and Imfinzi plus treme­li­mum­ab in com­bi­na­tion with chemother­a­py.


Im­age: Pas­cal So­ri­ot. AP IM­AGES

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

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Lisa Deschamps, AviadoBio CEO

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